President Trump has boasted that the treatment he has received for COVID-19 has cured him of the disease and made him feel better than ever. It’s very difficult to know whether that’s true, given how little we know about his condition, how unreliable his health reports have been and how experimental his course of treatment is. But we do know that these drugs often come with considerable side effects — side effects that could change the behavior of the leader of the free world.
In particular, one of the drugs he has been given, dexamethasone, can cause psychiatric side effects, which has raised concerns. Of course, just because side effects could affect behavior doesn’t mean they are doing so.
“We need to exercise caution in attributing any particular form of behavior to side effects of medication,” said Edward Shorter, a medical historian at the University of Toronto. “Trump has such a long history of bizarre and erratic behavior that the latest manifestation of it need not be a medication side effect at all.”
Rather than jumping to conclusions, it’s helpful to take a step back and consider what the science tells us about these therapeutics. Let’s run through the three major drugs doctors have prescribed to Trump and what their side effects might be.
Regeneron: Little is known
This antibody cocktail is the treatment we know the least about, because it’s a new, experimental therapeutic that has not yet been approved by the U.S. Food and Drug Administration. Regeneron has conducted a drug trial of its treatment — which uses lab-grown, antibodies specific to the novel coronavirus to help fight off an infection — but the results have not been published, aside from a promising press release from the company last week. The release didn’t mention any potential side effects. We do know the cocktail is administered intravenously, and any IV treatment can potentially cause certain side effects like fever and chills. But other than that, until more details are published, it’s hard to say whether the cocktail changed anything for the president, including his claims of it “curing” him.
Remdesivir: Mostly mild side effects
This antiviral drug was originally developed in 2009 as a potential treatment for hepatitis-C. While it didn’t prove effective for that disease, early trials in the COVID-19 pandemic found it could reduce the duration of infection and increase the likelihood of survival. It was authorized for emergency use by the FDA in May.
While there is still work to be done to learn the full scope of the drug’s effects, so far the most common side effects reported, such as nausea and constipation, are mild. Some COVID-19 patients have experienced more severe symptoms while taking remdesivir, including worsening respiratory failure and high levels of certain enzymes in the liver, which can cause damage, but these are more rare. In a phase 3 trial of remdesivir published in May, 8 percent of patients experienced worsening respiratory distress and 7 percent had elevated enzymes in their liver. But because the research on this drug is still limited, we don’t fully understand the link between the drug and these adverse effects.
“Even though any drug can have side effects, including remdesivir, on balance it doesn’t have a lot,” said Dr. Rajesh Gandhi, an infectious diseases physician at Massachusetts General Hospital and Harvard Medical School. “It can have effects on the liver occasionally, which is why we routinely do liver checks and I’m sure the president is having routine liver checks.”
Indeed, in a briefing on Sunday, Trump’s physicians said they’re monitoring the president’s liver functions, which are indicating “normal findings.” (Though we don’t know to what norm they’re comparing Trump’s levels. Normal for a COVID-19 patient, or normal for a healthy person?) On Monday, his doctors said Trump was given a five-day course of remdesivir, with the final dose on Tuesday.
Dexamethasone: A long list of side effects
We know the most about this drug because it’s been around for half a century, and perhaps as a result it comes with the longest list of possible side effects, ranging from acne and hair growth to severe psychiatric effects. This is typical for corticosteroids like dexamethasone — they’re versatile and effective but also can wreak all kinds of havoc on the body and mind. Corticosteroids are synthetic versions of hormones the body naturally produces and are effective in reducing inflammation. For this reason, they’re typically used to treat conditions such as lupus and rheumatoid arthritis. But dexamethasone has also been found to be effective in treating COVID-19 in cases in which the patient required oxygen or ventilation.
Naturally, the potential psychiatric side effects are concerning given Trump’s job. Nobody wants the guy with the nuclear codes to be experiencing psychosis. But we don’t have a great understanding of how common the psychiatric effects are.
“This has not been widely studied because dexamethasone largely went out of style,” Shorter said.
A meta-analysis published in 2006 (the most recent I could find) looked at psychiatric side effects of corticosteroids broadly. The analysis found that studies have placed the rate of psychiatric side effects at everything from 1.8 percent to 57 percent, a range the authors chalk up to both the lack of understanding and the different definitions used. If someone has a bit of trouble falling asleep while taking a steroid, one researcher might consider that an adverse psychiatric event, while another might not even clock it. Another review, from 1983, reported a similar range, with adverse effects occurring in from 1.6 percent to 62 percent of patients, depending on the study.
But those figures include the full range of psychiatric symptoms, and the majority of those reported are mild or moderate — the 1983 review found severe effects occurred only 5 percent of the time. Even mania, which sounds concerning, can manifest in a mild way that basically just means the patient feels a little more energetic or “revved up,” according to Ghandi. That’s not to say that the more severe side effects aren’t worth paying attention to. Some patients experience serious psychiatric impacts from these drugs, including hallucinations and psychosis — a case study published last year described a patient who received just one 5 mg shot of dexamethasone and then experienced such intense psychosis he tried to cut out his own testicle with a kitchen knife.
While it’s not totally clear how often these side effects occur, we do know they typically have a lot to do with dose and duration. The higher the dose, and the longer a person is on it, the higher the risk of adverse effects. The trials of dexamethasone for COVID-19 recommended no more than 10 days on the drug, at a dose of 6 mg per day, which would be on the lower end of the risk range.
Trump’s age and sex don’t put him at any higher risk for these adverse effects, either. Studies have found no link between age and psychiatric side effects and when it comes to sex, women are at a slightly higher risk than men.
Even if Trump has not had any side effects yet, there is a risk that some could still develop. What research we do have shows that these symptoms can arrive after several days, and sometimes last for weeks, even after completing the course of the drug.
“The vast majority of these patients develop symptoms less than two weeks from [the first dose] and more typically three or four days after the initiation of corticosteroid therapy,” the 2019 case study read. “In most cases, any associated delirium commonly resolves within days and psychosis within a week, though depression or manic symptoms may last up to six weeks after discontinuation of steroids.”
On Monday, Trump’s doctors said he was “continuing” dexamethasone, but it’s unclear how long he will be receiving the drug. On Friday, he told reporters he was not currently taking any medication for COVID-19.
“He’s probably no longer on it, is my guess,” said Dr. David Juurlink, the head of clinical pharmacology and toxicology at Sunnybrook Health Sciences Centre in Toronto. “The study that guided our decision-making on that was up to 10 days, and it was only patients who needed oxygen.”
Of course, all of these statistics are averages, and each individual patient is different. Understanding the risks associated with the drugs can provide useful context, but without more transparency from Trump and his doctors, it’s impossible to guess what, if any, side effects he may be experiencing.